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Comprehensive androgen-dependent transcriptome analysis in human genital tissue.

Radhika Sivaprasad1, Kristian Händler2, Almuth Caliebe1

  • 1Institute of Human Genetics, University Hospital of Schleswig-Holstein, Kiel University, Kiel, Germany.

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|November 18, 2025
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Summary
This summary is machine-generated.

Androgen receptor (AR) signaling is vital for male development. This study identified new AR target genes in human genital skin fibroblasts, enhancing understanding of androgen insensitivity syndrome (AIS) and related conditions.

Keywords:
Androgen insensitivity syndromeAndrogen receptorTranscriptional regulation

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Area of Science:

  • Endocrinology
  • Genetics
  • Molecular Biology

Background:

  • Androgen receptor (AR) signaling is essential for male genital development.
  • Disruptions in AR signaling cause androgen insensitivity syndrome (AIS), often due to unknown genetic factors.
  • Understanding androgen-dependent gene expression in human genital tissues is crucial.

Purpose of the Study:

  • To investigate androgen-dependent transcriptional changes in human genital skin fibroblasts (GSFs).
  • To identify novel androgen receptor (AR) target genes in human genital tissue.
  • To elucidate the genetic mechanisms underlying androgen insensitivity syndrome (AIS).

Main Methods:

  • Transcriptomic profiling of foreskin- and scrotum-derived GSFs treated with dihydrotestosterone.
  • Differential gene expression analysis to identify up-regulated genes.
  • Androgen response element motif scanning to confirm direct AR binding.

Main Results:

  • Identified 409 and 260 up-regulated genes in foreskin- and scrotum-derived GSFs, respectively.
  • GSFs from individuals with complete AIS showed no androgen response, confirming AR dependency.
  • Confirmed direct AR binding in key genes (e.g., AOX1, APOD, FKBP5, FAM107A) involved in neuronal, muscle, cardiovascular, and sex development pathways.

Conclusions:

  • Discovery of new AR target genes expands knowledge of androgen signaling pathways.
  • This research aids in understanding the etiology of AIS and other androgen-related disorders.
  • Provides a foundation for further investigation into AR-mediated gene regulation in human development.